In these studies, we will define the contribution of proinsulin and pro-insulin conversion products to circulating insulin-like-immunoreactivity in impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) by application of sensitive and specific immunoassays, ELISA, IRMA, and HPLC techniques. The relationships between qualitative and quantitative alterations in insulin secretion and alterations in the biochemical composition of beta-cell secretory products will be explored in these conditions using our previously validated approach to derive accurate estimates of pancreatic insulin secretion rates by deconvolution of peripheral C-peptide.